Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

$,xF
H3q
1 ) euLi
2) il. Me O$~*b
Scheme 1.14
U
H2,,.&Ef32~e f L-AiaOMe
This approach was then applied to the synthesis of a-amino acids by forming a
bis-lactim ether 1.33 from L-ValGly. A number of electrophiles were added, to give
after hydrolysis, D-amino acid methyl esters in 75-959 ee, with 62-9196 yields for the
addition and 5249% yields for the hydrolysis to the methyl ester (Scheme 1. 15).39
Stereocontrol at the Pcarbon is less impressive, with only 22% de when chiral halide
electrophiles were used? Furthemore, when the Li-enolate of 1.33 was added to
carbonyl electrophiles, only 10-75 % de was achieved, although exchanging the Iithium
enolate to a titanium derivative increased the diastereoselectivity to >95% de with >95%
ee and yields of between 77-93%.41 A major disadvantage of the method. however, is the
necessity to separate the two amino acid methyl esters that are generated as a result of
hydrolysis of bis-lactim template.
Scheme 1.15
R = n-heptyi. CH2eCH,
CH2CH=CHF+h, En
-k L-Val-OMe